Abstract
THERE are now about 60 examples of reactions that have been successfully catalysed by monoclonal antibodies1–3. Not surprisingly, many of the early examples involved reactions that were already favoured kinetically (such as carbonate and ester hydrolysis). But it has since been shown that antibodies can also accelerate reaction pathways that are normally disfavoured kinetically (by at least a few kcal mol–1)4–7. Here we use transition-state theory to provide a quantitative analysis of the scope and limitations of antibody catalysis. We show that the observed rate accelerations can be predicted from the ratio of equilibrium binding constants of the reaction substrate and the transition-state analogue used to raise the antibody. This scheme allows us to rationalize the product selectivity displayed in antibody catalysis of disfavoured reactions, to predict the degree of rate acceleration that catalytic antibodies may ultimately afford, and to highlight some differences between the way that they and enzymes catalyse reactions.
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Stewart, J., Benkovic, S. Transition-state stabilization as a measure of the efficiency of antibody catalysis. Nature 375, 388–391 (1995). https://doi.org/10.1038/375388a0
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DOI: https://doi.org/10.1038/375388a0
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